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OBJECTIVE The current study analysed the viral safety among Iranian blood donors. BACKGROUND Plasma products demand is increasing in the world. With contract plasma fractionation, the plasma wastage decreases and the access of patients to plasma-derived medicines (PDM) improves. STUDY AND DESIGN METHOD Screening results including hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (HCV), and human immunodeficiency virus (HIV) Ag/Ab of 19 054 036 donations from 2006 to 2015 were analysed. The plasma for fractionation was tested for HBV DNA, HCV RNA, HIV RNA, HAV RNA, and Parvovirus B19 DNA by fractionators. New samples were collected from the positive donors and retested. The prevalence of serological and nucleic acid testing (NAT) markers per 105 donations, 95% confidential interval (CI), and p-values were calculated. RESULTS The prevalence of markers was as follows: 250/105 donations for HBsAg from 516 in 2006 to 116/105 donations in 2015; 74/105 donations for HCV, decreasing from 127 to 41/105 and 3.6/105 for HIV during current study. During 10 years, 5 713 641 units of recovered plasma were shipped for contract fractionation to produce PDM; 0.26/105 donations for HBV DNA and 0.14/105 for HCV RNA were reported positive. The results of five retested samples for HBV and one sample for HCV were negative. CONCLUSION The prevalence of HBV, HCV, and HIV in blood donations was extremely low. Thanks to the availability, high quality and safety of recovered plasma as a result of the improvements in the quality system at IBTO, this plasma could be used for the production of PDMPs.

Background and Aim: Blood malignancies, one of the most common cancers in the world, cause a large number of deaths each year. Many inherited and acquired factors are involved in the development of this disease. Exosomes are a very small model of cells that are secreted by most cells in the body under physiological and pathological conditions. On the other hand, they have found a special place in the treatment of these diseases because of their very small structure and biodegradability. Materials and Methods: This study is a systematic review article. For this study, the electronic databases such as PubMed, Scopus and Web of Science were reviewed and 110 original and review articles were studied from 2000 to 2020. Exosome, blood malignancies and immunotherapy were used as keywords along with a number of other related terms such as tumor microenvironment, acute myeloid leukemia, acute lymphoid leukemia, chronic lymphoid leukemia and multiple myeloma (Exosome AND Leukemia, Leukemia AND Immunotherapy, Exosome AND Cancer, AML AND Exosome) to search in these databases. Finally, 51 sources that related to exosomes and myeloid and lymphoid blood malignancies were used. Results: The genomic profile of malignant cells and tumor microenvironment changes in the conditions of the disease. The contents of exosomes released by leukemic cells, including anti-apoptotic proteins, various microRNAs, angiogenic agents, heat shock proteins and oncogenes involved in the development of inflammatory phenotype in the target cells, are known as factors involved in the pathogenesis of leukemia. A variety of therapeutic materials such as anti-inflammatory drugs, recombinant proteins, siRNA and the inhibitor of various microRNAs can also be packaged in the exosomes with several ways and used to treat leukemia. Conclusion: Exosomes derived from malignant cells play the important role in the growth and proliferation, angiogenesis, metastasis, resistance to chemotherapeutic agent, and the escape of cancer cells from the immune system by the modification of tumor microenvironment. The role of exosomes in the creation and development of blood malignancies has been proven. Therefore, using of them will probably be very helpful and promising in the treatment of these disorders with various forms.

Background/objective Hemophilia A is a genetic disorder through which patients suffer from recurrent bleeding. This can be caused by a defect in human plasma coagulation factor VIII. High incidence of FVIII inhibitors in some severe hemophilia A patients after FVIII therapy is a considerable complication. Determination of good predictive factors can improve the safety of this treatment. HLA-II have been shown as a predictive element for inhibitor development. The goal of this study is to determine the association between HLA-DRB1*15:03, HLA-DRB1*11 and HLA-DRB1*01:01 alleles and FVIII inhibitors in severe hemophilia A patients in Iran. Materials/methods HLA-DRB1 genotyping was performed using Multiplex sequences Specific Primers (PCR-SSP) in two groups of severe hemophilia A patients comprising 51 and 50 individuals with and without FVIII inhibitors respectively. The levels of inhibitor were determined through Nijmegen-modified Bethesda assay. HLA-DRB1 allele frequencies were compared between groups by using multiple logistic regression models. Results HLA-DRB1*01:01 allele frequency was significantly higher in patients without inhibitor ORadj: 2.7 (95%CI: 1.08, 6.97; P = 0.034). There wasn’t any statistically significant difference in HLA-DRB1*11 allele frequency between groups ORadj: 0.7 (95%CI: 0.27, 1.82; P = 0.47). There was no connection between HLA-DRB1*15:03 and inhibitor development ORadj: 0.94 (95%CI: 0.38, 2.35; P = 0.94). Conclusion An association between HLA-DRB1*01:01 and paucity of FVIII inhibitor showed that this allele has probably a protective effect in severe hemophilia A patients in Iran. Determination of the predictive and protective alleles are beneficial in pre-treatment activities and decrease the risk of unsuccessful therapy with FVIII in each population.

Background: An analysis of red blood cell alloimmunization in patients with thalassemia can help to devise specific strategies to decrease the alloimmunization rate. This study explored the frequency and specificity of alloantibodies and autoantibodies against red blood cell (RBC) antigens in patients with thalassemia referring to the Iranian Blood Transfusion Organization (IBTO) Immunohematology Reference Laboratory (IRL) in Tehran. Materials and Methods: This study first examined the laboratory records of 23,113 patients suffering from different diseases referring to IBTO’s IRL for pretransfusion testing in the 2008-2015 period. ABO and Rh(D) typing and antibody screening tests were performed for all 23,113 patient records and 685 (2.97%) beta-thalassemia patients with positive pre-transfusion test results (antibody screening and/or DAT) were selected for further investigation. Results: The antibody screening test was positive in 640 out of 685 thalassemic patients (93.4%). DAT was performed for 529 patients, 226 (33%) of which showed positive results. Meanwhile, 161 out of 685 beta-thalassemia patients (23.5%) had positive auto control test results, reflecting the possible presence of allo- and/or autoantibodies. The most common antigen-specific alloantibodies were directed against K and E RBC antigens with a frequency of 25% (Anti-K) and 11.91% (Anti-E), respectively. The development of two antibodies (double antibodies) in one patient was observed in 80 individuals (11.46%). Conclusion: Age, gender, history of pregnancy, and splenectomy were not contributing factors to the antibody presence in the patient population under study. Extended red blood cell phenotyping should be considered as an essential procedure for expected multi-transfused thalassemia patients before blood transfusion. Considering the high frequency of anti-K and anti-E observed in this study, it is recommended that thalassemia patients in Iran are tested through phenotyping of RBC units for K and E antigens before transfusion.

The bearing capacity of a pile group mostly depends on parameters of the soil shear strength affected by the soil-water characteristics, especially in unsaturated soils. The soil shear strength is entirely affected by hydraulic stresses in unsaturated soil, such as precipitation and evaporation. Further, the bearing capacity of the pile installed on unsaturated soil depends on hydraulic stresses applied to the soil. Furthermore, slope vicinity may cause a severe decline in the pile bearing capacity. The present study aimed to investigate a pile group in unsaturated soil adjacent to a slope and analyzed the effect of the rainfall on the soil strength parameters. Thus, a numerical study has been performed using a finite difference software,i.e., FLAC2D. Besides, to investigate the model in a real situation, the intensity and duration of rainfall are considered to evaluate changes in hydraulic stresses. Finally, the results show that the rainfall causes a considerable decrease in soil strength parameters in unsaturated soil, leading to the reduction of the pile group bearing capacity and slope stability.

The unique properties of gold nanoparticles, their rich surface chemistry, and low toxicity as well as easy methods of synthesis have promoted conjugation of the particles with numerous biomolecules for site-specific delivery. Gold nanoparticles have multiple applications including photoablation, diagnostic imaging, radiosensitization, vaccine development, antioxidant, and multifunctional drug-delivery vehicles.These applications require an increasingly complex level of surface decoration in order to achieve efficacy, and limit off-target toxicity. This review will discuss the chemical and physical approaches commonly utilized in relation to surface decoration and the powerful system used to indicate success of the conjugation. Finally, we review the range of recent studies about covalent and noncovalent modes for conjugation of antibodies to the particle surface that aim to advance gold nanoparticle treatments and diagnostics toward the clinic. Keywords: Gold nanoparticle, Bioconjugation, Chemical interaction, Physical interaction-covalent mode, Noncovalent mode

Background The information about the dynamics of blood collection, components preparation and distribution in Iran was measured and compared during 2008–2012. Study designs and methods The survey instruments were based on collecting data from all 220 blood collections and blood processing centers over the country, registering them in the validated data base and reporting them to headquarter of Iranian Blood Transfusion Organization. Results Total blood collection increased during this period, and in 2012 represented a 12.6 percent increase compared to that in 2008. On average, red blood cells, fresh frozen plasma and platelet concentrate were prepared from 95.5 ± 2.4, 81 ± 3.8 and 47 ± 8.8 percent of all whole blood collection. From 2008 to 2011, the distribution of whole blood and fresh frozen plasma revealed different patterns. For whole blood, declines were noted, while for fresh frozen plasma increases were reported. In addition the distribution of red blood cells and platelet concentrate did not change considerably. Also between 2008 and 2012, the mean percentage of outdated and discarded units was 3.6 ± 1 and 5.2 ± 4.6. Conclusion This study as a first national survey provides comprehensive information about the blood supply, components preparation and distribution, and helps to define strategy for the future.

Although blood components are precious resources, their wastage is still a problem in hospitals all over the world. As no comprehensive study has evaluated hospital wastage in Iran, the main aim of the study was to identify the wastage as a percentage of issue during 2005-2015 and the secondary objective was to focus on the reasons of the blood components wastage.Wastage as a percentage of issues was calculated for red blood cells, plasma and platelet concentrate separately. Also, for each product, the percentage of wastage was calculated as the number of units wasted for each reason divided by the total number of units wasted.The wastage rate of red blood cells, plasma and platelet concentrate was 5.7 ± 0.7, 1.4 ± 0.4, and 3.2 ± 0.5, respectively. The main cause of red blood cells, plasma, and platelet concentrate wastage was date expiry and reserved/returned units of operating room and or ward. In 2015 compared to 2005, despite a significant decrease (p value0.0001) in red blood cells and plasma expired units, there was a remarkable increase in expired PC units (p value0.0001). In contrast to expired units, there was a significant increase (p value0.0001) in reserved/returned units of operating room and or ward for red blood cells and plasma.Time expiry and reserved/returned from operating room were the most important reasons of blood component wastage. The percentage of wastage could be decreased by implementing MSBOS program and designing a software application for efficient management of reserved hospital inventories.

Plasma is the liquid part of blood. It is estimated 21.6 million liters of plasma collect from Whole blood annually. From these plasma, 4.2 million liters transfuse, 8.1 million liters fractionate, 9.3 million liters waste. Nowadays, blood products and PDM (plasma derived medicine) consider as essential medicine in modern health care and transfusion medicine. Iranian blood transfusion organization as a non-profit organization was established in 1974 in order to centralize all blood transfusion activities from donor recruitment to distribution of blood components to hospitals. Iran is the only country in EMR region with the rate of 20-29.9 blood donations per 1000 population and reached 100% voluntary non-remunerated blood donation in 2007. RBCs and platelets demand are much more than FFPs so the IBTO was faced the surplus plasma that could cause surplus plasma wastage. Simultaneously, hospitals need more plasma derived medicine especially albumin, IVIG, factor VIII, factor IX. IBTO was faced the challenges such as Fractionators selection, Plasma volume shipment, Contract duration, Product profile, Multiple External audits, Cold chain maintenance, Transporting plasma across international borders, NAT test. To overcome plasma wastage and storage of PDM. IBTO involved toll manufacturing in 2005 and not only prevents plasma wastage but also save MOH (ministry of health) budget.

Recent epidemiological evidences revealed the higher prevalence of 'O' blood group in the residents of malaria-endemic areas. Also some data indicated preference of mosquitoes to 'O' group. The aim of this study was to determine ABO group ratio in the residents as well as ABO group preference of Anopheles in two malaria endemic areas in south of Iran. Agglutination method was used for ABO typing of residents. Field blood fed Anopheles specimens were tested against vertebrate DNA using mtDNA-cytB PCR-RFLP and then the human fed specimens were tested for ABO groups using multiplex allele-specific PCR. A total of 409 human blood samples were identified, of which 150(36.7%) were 'O' group followed by 113(27.6%), 109(26.7%), and 37(9.0%) of A, B, and AB groups respectively. Analyzing of 95 blood fed mosquitoes revealed that only four Anopheles stephensi had fed human blood with A(1), B(1), and AB(2) groups. Result of this study revealed high prevalence of O group in south of Iran. To our knowledge, it is the first ABO molecular typing of blood meal in mosquitoes; however, due to low number of human blood fed specimens, ABO host choice of the mosquitoes remains unknown. This study revealed that ABO blood preference of malaria vectors and other arthropod vectors deserves future research.

Prostate-specific antigen (PSA) is used to screen for prostate disease, although it has several limitations in its application as an organ-specific or cancer-specific marker. Furthermore, a highly specific/sensitive and/or label-free identification of PSA still remains a challenge in the diagnosis of prostate anomalies. We aimed to develop a gold nanoparticle (GNP)-conjugated anti-PSA antibody-based localized surface plasmon resonance (LSPR) as a novel approach to detect prostatic disease. A total of 25 nm colloidal gold particles were prepared followed by conjugation with anti-PSA pAb (GNPs-PSA pAb). LSPR was used to monitor the absorption changes of the aggregation of the particles. The size, shape and stability of the GNP-anti-PSA were evaluated by dynamic light scattering transmission electron microscopy (TEM) and zetasizer. The GNPs-conjugated PSA-pAb was successfully synthesized and subsequently characterized using ultraviolet absorption spectroscopy and TEM to determine the size distribution, crystallinity and stability of the particles (for example, stability of GNP: 443 mV). To increase the stability of the particles, we pegylated GNPs using an N-(3-dimethylaminopropyl)-N*-ethylcarbodiimide hydrochloride (EDC)/N-hydroxylsuccinimide (NHS) linker (for example, stability of GNP after pegylation: 272 mV). We found a significant increase in the absorbance and intensity of the particles with extinction peak at 545/2 nm, which was shifted by ~1 nm after conjugation. To illustrate the potential of the GNPs-PSA pAb to bind specifically to PSA, LSPR was used. We found that the extinction peak shifted 3 nm for a solution of 100 nM unlabeled antigen. In summary, we have established a novel approach for improving the efficacy/sensitivity of PSA in the assessment of prostate disease, supporting further investigation on the diagnostic value of GNP-conjugated anti-PSA/LSPR for the detection of prostate cancer.

IVIG can be prepared from fractionation of normal human plasma and it is used as a therapeutic drug for treatment of various diseases. IVIG has been for some time the high-growth product within the plasma derived products, at both a global and a national country level. Fractionation was performed according to Cohn method with some modifications. Fraction II was first produced and then it was used for purification and virus inactivation steps. Two methods of virus inactivation (pasteurization at 60 degrees C for 10 hours and solvent/detergent treatment with TnBP and Tween 80) were used and validated. A chromatography method (cation exchange chromatography on CM Sepharose FF) was also added to obtain high purity. The final product (in liquid and freeze dried formulation) meets European Pharmacopeias requirements. The amount of PKA and aggregates was beyond the acceptance limit. The intactness of the IVIG was also examined by circular dichroism (secondary and tertiary structure). It was stable after 6 months of storage. Since Iran market is completely dependant on importation of plasma derived products, it is important to develop such methods for production of IVIG to obtain regional demands.

The utilization of umbilical cord blood transplantation (UCBT) has been increasing because of the potential advantage of rapid accessibility and the lesser risk of graft-versus-host disease (GVHD), thus allowing less strict HLA matching. IL-28A, also known as IFN-lambda2, has been regarded as a member of a new cytokine family that shares some features with type I interferon (IFN) and was shown to have antiviral activity. The aim of this study was to identify biological activity of IL-28 on cord blood CD4(+) T cells.In this study, we cultured CD4(+) T cells with IL-28A (20 ng/ml), IL-2 (20 ng/ml) and 5microg/ml MACS Anti-Biotin MACSiBead Particles (bead-to-cell ratio 1:2) for 2 weeks.Flow cytometry analyses showed that IL-28A cannot be effective on CD25 and Foxp3 expression on cord blood CD4(+) T cells, and it is not involved in proliferation of these cells. Treg suppression assay also showed that this cytokine cannot induce production of regulatory T cells.We showed that IL-28A is not involved in expression of CD25 and Foxp3 markers and proliferation of CD4(+)CD25(-) T cells, and that our findings also suggest that induction of Foxp3 in T cells activated by anti-CD3/anti-CD28 does not result in the regulatory activity in these cells.

The safety of plasma derived medicinal products, such as immunoglobulin, depends on viral inactivation steps that are incorporated into the production process. Several attempts have been made to validate the effectiveness of these inactivation methods against a range of physio-chemically diverse viruses. Treatment with solvent/detergent (S/D) and pasteurization (P) has been continuously used in our IgG production and these methods were analysed in this study as models of viral inactivation. Bovine Viral Diarrhoea Virus (BVDV), Herpes Simplex Virus (HSV) and Vesicular Stomatitis Virus (VSV) were employed as models of HCV, HBV and HIV respectively. Polio and Reo viruses also were used as stable viruses to chemical substances. The infectivity of a range of viruses before and after treatment with two methods of viral inactivation was measured by end point titration and their effectiveness expressed as Logarithmic Reduction Factors (LRF). Solvent/detergent treatment reduced the amount of enveloped viruses by 5-6 logs. The reduction factor was between 5-6 logs for all viruses used in the pasteurization process. A final log reduction factor was obtained as the sum of the two individual methods. Both inactivation methods have advantages and disadvantages with respect to their ability to inactivate viruses. Thus,combination of two robust virus inactivation steps, solvent/detergent and pasteurization, increases the safety margin of immunoglobulin preparations.

Cytokines have been introduced as critical inducers in the development of Th subpopulations.Cytokines like IL-10 are involved in inducing regulatory T cells such as Type 1 regulatory T (Tr1) cells cells. IL-22 is a member of IL-10 family of cytokines, and IL-28A is a member of IFN-γ family. In this study, cord blood mononuclear cells (CBMC) from normal healthy individuals were isolated by Ficoll and then naïve T cells were purified by CD4+CD25+ Regulatory T cell Isolation kit. The effect of these two cytokines on production of IL-5, TGF-β, IL-10, IL-4 and IFN-γ cytokines from cord blood T cells was investigated to identify Tr1 cells as well as Th1 and Th2 polarization. Flow cytometric analysis showed that IL-28A and IL-22 were not effective in expression of IL-5 and TGF-β either alone or in synergy, but in view of IL-10, IL-4 and IFN-γ, the results showed that IL-22 increased IL-10 and IL-4 but had a decreasing effect on IFN-γ. The results showed that IL-28A was not effective in increasing or decreasing the level of IL-10, IL-4 and IFN-γ. Therefore, according to these results, IL-22 and IL-28A were not effective in inducing Tr1 cells.

Recent epidemiological evidences revealed a higher rate of O blood group in the residents of malaria-endemic areas suggesting that groups A, B, and AB associated with a higher disease severity and fatality. Also recent data showed the low prevalence of AB group within the malaria-endemic residents in south of Iran and India. The aim of this study was to determine the ABO blood groups preference of Anopheles stephensi which is the main malaria vector in Iran, southwest Asia, and India. An. stephensi mosquitoes were fed either artificially on A/B/O/AB membrane blood feeders or directly on human volunteer hands and forearms of A/B/O/AB groups in a cage under lab conditions. Phenotype and genotype analyzes of 450-blood-fed mosquito specimens using agglutination and multiplex-allele-specific PCR revealed a significant blood preference of An. stephensi to AB group (40%) than other groups of A (24%), B (21%), and O (15%) in combination of both experiments. High preference of An. stephensi to AB group might increase malaria infection and fatality in this blood group and resulted in low frequency of AB group in the residents of malaria endemic areas. The data suggested that malaria vectors, like parasites may have selection pressure on human genotypes.

There have been several reports using various superparamagnetic iron oxide (SPIO) nanoparticles to label mammalian cells for monitoring their temporal and spatial migration in vivo by Magnetic Resonance Imaging (MRI). The purpose of this study was to evaluate the efficiency of labeling cells using two commercially available FDA-approved agents: ferumoxide, a suspension of dextran-coated SPIO used as an MRI contrast agent and protamine sulfate used ex vivo as a cationic transfection agent to evaluate the use of clinical 1.5 Tesla magnetic resonance imaging equipment in showing the in vivo homing of iron oxide-labeled human CD34+ cells in irradiated mouse. After labeling human Hematopoietic (CD34+) stem cells with ferumoxide-protamine sulfate complex (FE-Pro), cellular toxicity, functional capacity and quantitative cellular iron incorporation were determined. FE-Pro labeled cells demonstrated neither short or long-term toxicity nor changes in colonogenic assay of the stem cells and their phenotype when compared with unlabeled cells. Efficient labeling with FE-Pro was observed with iron content per cell varying between 1.91 +/- 0.1 pg for CD34+ cells with 100% of cells labeled. After irradiation, Female Balb/c mice underwent MR imaging before and 12, 24, 48 and 72 h after intravenous injection of 0.5-1.5 x 10(7) labeled CD34+ cells. A significant decrease in MR signal intensity was observed in bone marrow at 24 and 48 h after injection. Our observations confirm that efficient labeling of cells with appropriate contrast agents should facilitate the translation of this method to clinical trials for evaluating the trafficking of infused or transplanted cells by MR Imaging.

The safety of plasma derived medicinal products, such as immunoglobulin, depends on viral inactivation steps that are incorporated into the production process. Several attempts have been made to validate the effectiveness of these inactivation methods against a range of physio-chemically diverse viruses. Treatment with solvent/detergent (S/D) and pasteurization (P) has been continuously used in our IgG production and these methods were analysed in this study as models of viral inactivation. Bovine Viral Diarrhoea Virus (BVDV), Herpes Simplex Virus (HSV) and Vesicular Stomatitis Virus (VSV) were employed as models of HCV, HBV and HIV respectively. Polio and Reo viruses also were used as stable viruses to chemical substances. The infectivity of a range of viruses before and after treatment with two methods of viral inactivation was measured by end point titration and their effectiveness expressed as Logarithmic Reduction Factors (LRF). Solvent/detergent treatment reduced the amount of enveloped viruses by 5-6 logs. The reduction factor was between 5-6 logs for all viruses used in the pasteurization process. A final log reduction factor was obtained as the sum of the two individual methods. Both inactivation methods have advantages and disadvantages with respect to their ability to inactivate viruses. Thus,combination of two robust virus inactivation steps, solvent/detergent and pasteurization, increases the safety margin of immunoglobulin preparations.

Platelet transfusion is accompanied by febrile nonhemolytic transfusion reactions. The generation of cytokines (like IL-1 beta, IL-6, IL-8, and TNF-alpha) in platelet concentrates by white cells is suggested to be responsible for febrile nonhemolytic transfusion reactions. The number of white cells in the platelet concentrates is crucial to cytokine generation.This study was performed to determine whether WBC reduction in platelet concentrates by prestorage leukodepletion filters or inactivation by gamma radiation reduced the levels of these cytokines during storage for 3 days. Each of the platelet concentrates (n = 54) was prepared from a single random donor by platelet-rich plasma. This was then divided into four groups: 1) unfiltered, nonirradiated random-donner platelet concentrates (n = 13); 2) unfiltered, gamma-irradiated random-donner platelet concentrates (n = 16); 3) filtered, nonirradiated random-donner platelet concentrates (n = 14); and 4) filtered, gamma-irradiated random-donner platelet concentrates (n = 11). Cytokine levels in platelet concentrates supernatants were measured by ELISA kits according to the manufacturer's recommendations.Our results showed that IL-8 was detected in unfiltered, nonirradiated, and gamma-irradiated random-donner platelet concentrates but not in the filtered random-donner platelet concentrates. TNF-alpha was only detected in unfiltered, nonirradiated units. Compared with unfiltered platelet concentrates, prestorage filtration prevented a rise in the IL-8 and TNF-alpha on day 3 of storage. The concentration of IL-1 beta was lower than the minimum concentration value of the kit used for this purpose. IL-6 was detected only in 7 units of all filtered platelet concentrates on day 3.These data indicate that gamma irradiation can not prevent generation of IL-8 in platelet concentrates during storage, but prestorage leukoreduction of platelet concentrates can prevent accumulation of IL-6, IL-8, and TNF-alpha during storage.